Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-26848-x
Keywords
-
Categories
Funding
- Swiss National Science Foundation [31003A_163314]
- Swiss National Science Foundation (SNF) [31003A_163314] Funding Source: Swiss National Science Foundation (SNF)
Ask authors/readers for more resources
This study presents crystal structures of Dop in different functional states, providing insights into the catalytic mechanism of this enzyme. Pupylation and depupylation are reversible protein modification processes mainly acting in members of Actinobacteria.
Pupylation is a bacterial post-translational protein modification, where the small ubiquitin-like protein Pup is covalently attached to lysine side chains of target proteins, which is a reversible process and depupylation is catalysed by the depupylase enzyme, Dop. Here, the authors present crystal structures of Dop in different functional states, which together with biochemical experiments provide insights into the catalytic mechanism of this enzyme. Pupylation is the post-translational modification of lysine side chains with prokaryotic ubiquitin-like protein (Pup) that targets proteins for proteasomal degradation in mycobacteria and other members of Actinobacteria. Pup ligase PafA and depupylase Dop are the two enzymes acting in this pathway. Although they share close structural and sequence homology indicative of a common evolutionary origin, they catalyze opposing reactions. Here, we report a series of high-resolution crystal structures of Dop in different functional states along the reaction pathway, including Pup-bound states in distinct conformations. In combination with biochemical analysis, the structures explain the role of the C-terminal residue of Pup in ATP hydrolysis, the process that generates the catalytic phosphate in the active site, and suggest a role for the Dop-loop as an allosteric sensor for Pup-binding and ATP cleavage.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available